EVALUATION OF THE ROLE OF CLINICAL UNMET NEED IN HEALTH TECHNOLOGY ASSESSMENT DECISION-MAKING OF ONCOLOGY TRIALS WITHOUT DEMONSTRATED OVERALL SURVIVAL BENEFITS DUE TO TREATMENT CROSSOVER
Author(s)
Anandaroop Dasgupta, PhD1, Ankita Kaushik, PhD1, Jens Grueger, PhD2, Sumeet Attri, MPharm3, Sukriti Sharma, MSc3, Barinder Singh, RPh4, Billy Amzal, MBA, MPH, MSc, PhD5;
1Gilead Sciences Inc., Foster city, CA, USA, 2The CHOICE Institute, School of Pharmacy, University of Washington, Seattle, WA, USA, 3Pharmacoevidence, Mohali, India, 4Pharmacoevidence, London, United Kingdom, 5Phastar, Paris, France
1Gilead Sciences Inc., Foster city, CA, USA, 2The CHOICE Institute, School of Pharmacy, University of Washington, Seattle, WA, USA, 3Pharmacoevidence, Mohali, India, 4Pharmacoevidence, London, United Kingdom, 5Phastar, Paris, France
OBJECTIVES: Treatment crossover in oncology trials often confounds the interpretation of overall survival (OS), a key endpoint for health technology assessment (HTA) decisions. This systematic literature review (SLR) assessed how HTA bodies have given precedence to clinical unmet need, allowed reimbursement, and provided favourable appraisal even in the absence of OS benefit.
METHODS: Published reports (2013-2024) from HTA bodies of the UK (NICE), France (HAS), Germany (IQWiG), Australia (PBAC), and Canada (CDA) were systematically reviewed and assessed.
RESULTS: Out of 1,653 records screened, 146 product submissions that allowed treatment crossover were included. Of these, 78 product submissions were assessed under cost-effectiveness-based payer archetype (NICE, n=32; CDA, n=20; PBAC, n=26). Unmet need was explicitly highlighted in seven NICE submissions and was characterized as the lack of effective therapies, reflected by similar/numerically improved but statistically non-significant OS across niche populations (untreated PD-L1+ metastatic non-small cell lung cancer [mNSCLC], TA531; recurrent or metastatic renal cell carcinoma, TA512; untreated MSI-H/dMMR metastatic colorectal cancer [mCRC], TA709; PD-L1 ≥50% mNSCLC, TA770; hormone-relapsed metastatic prostate cancer, TA887). All product submissions were recommended, with the incremental cost-effectiveness ratio being the primary driver of the decision. Among 68 product submissions evaluated under clinical-effectiveness-based payer archetypes (IQWiG/G-BA, n=42; HAS, n=26), only two referenced unmet need, which was characterized by the absence of effective therapies. ALK-positive mNSCLC previously treated with crizotinib (A16-62), where no OS benefit was shown but considerable benefit existed in morbidity, safety, and quality of life; and first-line MSI-H/dMMR mCRC (A21-36), where no OS, morbidity, or quality-of-life benefit was demonstrated, although safety outcomes showed considerable added benefit.
CONCLUSIONS: Across HTA bodies, unmet need was acknowledged but only influenced decisions when supported by meaningful improvements in clinical or health economic outcomes. Unmet need strengthened cases for reimbursement, provided there was evidence of sufficient added clinical benefit or cost-effectiveness versus standard of care.
METHODS: Published reports (2013-2024) from HTA bodies of the UK (NICE), France (HAS), Germany (IQWiG), Australia (PBAC), and Canada (CDA) were systematically reviewed and assessed.
RESULTS: Out of 1,653 records screened, 146 product submissions that allowed treatment crossover were included. Of these, 78 product submissions were assessed under cost-effectiveness-based payer archetype (NICE, n=32; CDA, n=20; PBAC, n=26). Unmet need was explicitly highlighted in seven NICE submissions and was characterized as the lack of effective therapies, reflected by similar/numerically improved but statistically non-significant OS across niche populations (untreated PD-L1+ metastatic non-small cell lung cancer [mNSCLC], TA531; recurrent or metastatic renal cell carcinoma, TA512; untreated MSI-H/dMMR metastatic colorectal cancer [mCRC], TA709; PD-L1 ≥50% mNSCLC, TA770; hormone-relapsed metastatic prostate cancer, TA887). All product submissions were recommended, with the incremental cost-effectiveness ratio being the primary driver of the decision. Among 68 product submissions evaluated under clinical-effectiveness-based payer archetypes (IQWiG/G-BA, n=42; HAS, n=26), only two referenced unmet need, which was characterized by the absence of effective therapies. ALK-positive mNSCLC previously treated with crizotinib (A16-62), where no OS benefit was shown but considerable benefit existed in morbidity, safety, and quality of life; and first-line MSI-H/dMMR mCRC (A21-36), where no OS, morbidity, or quality-of-life benefit was demonstrated, although safety outcomes showed considerable added benefit.
CONCLUSIONS: Across HTA bodies, unmet need was acknowledged but only influenced decisions when supported by meaningful improvements in clinical or health economic outcomes. Unmet need strengthened cases for reimbursement, provided there was evidence of sufficient added clinical benefit or cost-effectiveness versus standard of care.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
HTA6
Topic
Health Technology Assessment
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Oncology